Pregnant woman are offered multiple marker serum testing for fetal Down syndrome (DS) in the second trimester as routine standard of care. However, serum markers are only a screening tool and not a diagnostic test. Thus, when patients are screen positive, they are offered amniocentesis to confirm the suspicion of fetal DS. These serum markers are nonspecific for DS and, as a result, this test is burdened with a significant false positive and false negative rate. . Consequently, the vast majority of patients with a positive test will undergo amniocentesis with the real possibility of fetal loss for an unaffected pregnancy. Our hypothesis is that microarray technology available at our center can by used to isolate differentially expressed genes from DS placentae. Our proposed strategy is to apply this high-throughput method of gene expression analysis to identify gene expression changes in placentae from pregnancies affected with Down syndrome, followed by characterization of these genes and their gene products. These findings will form the basis of a subsequent grant submission that will be directed towards the ultimate goal of our placental research program identification and development of specific protein assays for fetal Down syndrome. The specific aim of this current submission is to determine qualitative or quantitative differences in gene expression between DS and normal placentae using microarray chip technology, which will allow for the screening of thousands of genes at once. Differential expression revealed in the microarray studies will be confirmed by Northern blot analysis.